scholarly journals Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor B signaling pathway

Oncotarget ◽  
2017 ◽  
Vol 8 (13) ◽  
pp. 22059-22075 ◽  
Author(s):  
Fang Liu ◽  
Yuan Zhang ◽  
Tingting Men ◽  
Xingyue Jiang ◽  
Chunhua Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Proteomic Analysis ◽  
Gastric Cancer Tissue ◽  
Platelet Derived Growth Factor ◽  
Cancer Tissue ◽  
Factor B ◽  
Quantitative Proteomic Analysis ◽  
Novel Proteins

scholarly journals Activation of c-Met (hepatocyte growth factor receptor) in human gastric cancer tissue

2004 ◽  
Vol 95 (10) ◽  
pp. 803-809 ◽  
Author(s):  
Takao Inoue ◽  
Hiroaki Kataoka ◽  
Kouichiro Goto ◽  
Koki Nagaike ◽  
Ko Igami ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Growth Factor Receptor ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Human Gastric Cancer ◽  
Hepatocyte Growth Factor Receptor ◽  
Hepatocyte Growth

Association of DOCK6 with cancer stem cell development and as an independent prognostic factor of gastric cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 68-68
Author(s):  
Chia-Siu Wang ◽  
Chung-Ying Tsai ◽  
Kam-Fai Lee ◽  
Liang-Mou Kuo ◽  
Kwang-Huei Lin
Keyword(s):  
Gastric Cancer ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Cancer Stem Cell ◽  
Signaling Pathway ◽  
Tumor Tissue ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Depth Of Invasion ◽  
Itraq Proteomics

68 Background: The prognosis of advanced gastric cancer (GC) remains poor, and the key players in molecular pathogenesis are predominantly unknown at present. Methods: In order to identify novel prognostic factor of GC, we compared the data of iTRAQ proteomics from 6 GC samples with that of Oncomine database from 86 GC samples to intersect 122 high-expression proteins in gastric cancer tissue. The candidate biomarkers were further characterized in fresh GC tumor tissues compared with adjacent non-tumor tissue by using Q-RT-PCR, immunohistochemical staining and western blot. GC cells with depletion of DOCK6 were examined to identify downstream molecules and establish their effects on cell motility, invasion and gastric cancer stem cell (CSC) markers. The possible signaling pathway of DOCK6 were also investigated. Results: DOCK6 is identified as one of the potential GC biomarkers in iTRAQ proteomics. Our data confirm the overexpression of DOCK6 in GC tumor tissue compared with adjacent non-tumor tissue. In addition, the clinical data shows higher DOCK6 expression was positive correlated to depth of invasion, lymph node metastasis, vascular invasion and pathological stage. Furthermore, higher DOCK6 expression represented significantly shorter cumulative survival both in univariate and multivariate analysis for survival outcome. Depletion of DOCK6 repressed the cell migration, proliferation, sphere formation, anchorage-independent growth and tumorigenicity as well as gastric cancer stem cell (CSC) markers. In order to explore the downstream effector of DOCK6, we correlated thousands of gene with DOCK6 in three GC dataset published in the literature. The DOCK6 positive-correlated genes were subsequently analyzed by Metacore. They were significantly involved in WNT/β-catenin signaling pathway. Our result demonstrates nuclear b-catenin, as well as CD44, was decreased accompanied by depleting DOCK6. Moreover, the interaction between DOCK6 and β-catenin was observed in GC cells. Conclusions: Our studies unveil the role of DOCK6 in the self-renewal of CSC and propose DOCK6 as an independent marker of tumor progression.

scholarly journals Assignment of intrachain disulfide bonds in platelet-derived growth factor B-chain

1993 ◽  
Vol 268 (18) ◽  
pp. 13372-13377
Author(s):  
A. Ostman ◽  
M. Andersson ◽  
G. Bäckström ◽  
C.H. Heldin
Keyword(s):  
Growth Factor ◽  
Disulfide Bonds ◽  
Platelet Derived Growth Factor ◽  
Factor B

scholarly journals Transactivation of Platelet-Derived Growth Factor Receptor α by the GTPase-Deficient Activated Mutant of Gα12

2006 ◽  
Vol 26 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Rashmi N. Kumar ◽  
Ji Hee Ha ◽  
Rangasudhagar Radhakrishnan ◽  
Danny N. Dhanasekaran
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Dominant Negative Mutant ◽  
Dependent Manner ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT The GTPase-deficient, activated mutant of Gα12 (Gα12Q229L, or Gα12QL) induces neoplastic growth and oncogenic transformation of NIH 3T3 cells. Using microarray analysis, we have previously identified a role for platelet-derived growth factor receptor α (PDGFRα) in Gα12-mediated cell growth (R. N. Kumar et al., Cell Biochem. Biophys. 41:63-73, 2004). In the present study, we report that Gα12QL stimulates the functional expression of PDGFRα and demonstrate that the expression of PDGFRα by Gα12QL is dependent on the small GTPase Rho. Our results indicate that it is cell type independent as the transient expression of Gα12QL or the activation of Gα12-coupled receptors stimulates the expression of PDGFRα in NIH 3T3 as well as in human astrocytoma 1321N1 cells. Furthermore, we demonstrate the presence of an autocrine loop involving PDGF-A and PDGFRα in Gα12QL-transformed cells. Analysis of the functional consequences of the Gα12-PDGFRα signaling axis indicates that Gα12 stimulates the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway through PDGFR. In addition, we show that Gα12QL stimulates the phosphorylation of forkhead transcription factor FKHRL1 via AKT in a PDGFRα- and PI3K-dependent manner. Since AKT promotes cell growth by blocking the transcription of antiproliferative genes through the inhibitory phosphorylation of forkhead transcription factors, our results describe for the first time a PDGFRα-dependent signaling pathway involving PI3K-AKT-FKHRL1, regulated by Gα12QL in promoting cell growth. Consistent with this view, we demonstrate that the expression of a dominant negative mutant of PDGFRα attenuated Gα12-mediated neoplastic transformation of NIH 3T3 cells.

Molecular Targeting of Platelet-Derived Growth Factor B by Imatinib Mesylate in a Patient With Metastatic Dermatofibrosarcoma Protuberans

2002 ◽  
Vol 20 (17) ◽  
pp. 3586-3591 ◽  
Author(s):  
Brian P. Rubin ◽  
Scott M. Schuetze ◽  
Janet F. Eary ◽  
Thomas H. Norwood ◽  
Sohail Mirza ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
Dermatofibrosarcoma Protuberans ◽  
Response To Therapy ◽  
Platelet Derived Growth Factor ◽  
Response To Treatment ◽  
Resected Specimen ◽  
Factor B

PURPOSE: Dermatofibrosarcoma protuberans is caused by activation of the platelet-derived growth factor B (PDGFB) receptor, a transmembrane tyrosine kinase. We investigated the response of dermatofibrosarcoma protuberans to the tyrosine kinase inhibitor imatinib mesylate. PATIENTS AND METHODS: A patient with unresectable, metastatic dermatofibrosarcoma protuberans received imatinib mesylate (400 mg bid). Response to therapy was assessed by [18F]fluorodeoxyglucose (FDG) positron emission tomography, magnetic resonance imaging, and histopathologic and immunohistochemical evaluation. RESULTS: The patient was treated for 4 months with imatinib mesylate. The hypermetabolic uptake of FDG fell to background levels within 2 weeks of treatment, and the tumor volume shrank by over 75% during the 4 months of therapy, allowing for resection of the mass. There was no residual viable tumor in the resected specimen, indicating a complete histologic response to treatment with imatinib mesylate. CONCLUSION: Imatinib mesylate is highly active in dermatofibrosarcoma protuberans. The dramatic response seen in this patient demonstrates that inhibition of PDGFB receptor tyrosine kinase activity can significantly impact viability of at least one type of solid tumor.

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